Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling

Mathias Pawlak; David DeTomaso; Alexandra Schnell; Gerd Meyer zu Horste; Youjin Lee; Jackson Nyman; Danielle Dionne; Brianna M.L. Regan; Vasundhara Singh; Toni Delorey; Markus A. Schramm; Chao Wang; Antonia Wallrapp; Patrick R. Burkett; Samantha J. Riesenfeld; Ana C. Anderson; Aviv Regev; Ramnik J. Xavier; Nir Yosef; Vijay K. Kuchroo

doi:10.1016/j.immuni.2022.08.007

Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling

Mathias Pawlak, David DeTomaso, Alexandra Schnell, Gerd Meyer zu Horste, Youjin Lee, Jackson Nyman, Danielle Dionne, Brianna M.L. Regan, Vasundhara Singh, Toni Delorey, Markus A. Schramm, Chao Wang, Antonia Wallrapp, Patrick R. Burkett, Samantha J. Riesenfeld, Ana C. Anderson, Aviv Regev, Ramnik J. Xavier, Nir Yosef, Vijay K. Kuchroo

Research output: Contribution to journal › Article › peer-review

Abstract

Interleukin-23 receptor plays a critical role in inducing inflammation and autoimmunity. Here, we report that Th1-like cells differentiated in vitro with IL-12 + IL-21 showed similar IL-23R expression to that of pathogenic Th17 cells using eGFP reporter mice. Fate mapping established that these cells did not transition through a Th17 cell state prior to becoming Th1-like cells, and we observed their emergence in vivo in the T cell adoptive transfer colitis model. Using IL-23R-deficient Th1-like cells, we demonstrated that IL-23R was required for the development of a highly colitogenic phenotype. Single-cell RNA sequencing analysis of intestinal T cells identified IL-23R-dependent genes in Th1-like cells that differed from those expressed in Th17 cells. The perturbation of one of these regulators (CD160) in Th1-like cells inhibited the induction of colitis. We thus uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23R signaling as a pathogenic driver in Th1-like cells inducing tissue inflammation.

Original language	English
Pages (from-to)	1663-1679.e6
Journal	Immunity
Volume	55
Issue number	9
DOIs	https://doi.org/10.1016/j.immuni.2022.08.007
State	Published - 13 Sep 2022
Externally published	Yes

Keywords

IL-23
IL-23 receptor
T helper cell
Th1-like cell
autoimmunity
colitis
inflammation
inflammatory bowel disease
pre-clinical mouse model
single-cell RNA sequencing

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology
Infectious Diseases

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10.1016/j.immuni.2022.08.007

Cite this

Pawlak, M., DeTomaso, D., Schnell, A., Meyer zu Horste, G., Lee, Y., Nyman, J., Dionne, D., Regan, B. M. L., Singh, V., Delorey, T., Schramm, M. A., Wang, C., Wallrapp, A., Burkett, P. R., Riesenfeld, S. J., Anderson, A. C., Regev, A., Xavier, R. J., Yosef, N., & Kuchroo, V. K. (2022). Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling. Immunity, 55(9), 1663-1679.e6. https://doi.org/10.1016/j.immuni.2022.08.007

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title = "Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling",

abstract = "Interleukin-23 receptor plays a critical role in inducing inflammation and autoimmunity. Here, we report that Th1-like cells differentiated in vitro with IL-12 + IL-21 showed similar IL-23R expression to that of pathogenic Th17 cells using eGFP reporter mice. Fate mapping established that these cells did not transition through a Th17 cell state prior to becoming Th1-like cells, and we observed their emergence in vivo in the T cell adoptive transfer colitis model. Using IL-23R-deficient Th1-like cells, we demonstrated that IL-23R was required for the development of a highly colitogenic phenotype. Single-cell RNA sequencing analysis of intestinal T cells identified IL-23R-dependent genes in Th1-like cells that differed from those expressed in Th17 cells. The perturbation of one of these regulators (CD160) in Th1-like cells inhibited the induction of colitis. We thus uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23R signaling as a pathogenic driver in Th1-like cells inducing tissue inflammation.",

keywords = "IL-23, IL-23 receptor, T helper cell, Th1-like cell, autoimmunity, colitis, inflammation, inflammatory bowel disease, pre-clinical mouse model, single-cell RNA sequencing",

author = "Mathias Pawlak and David DeTomaso and Alexandra Schnell and \{Meyer zu Horste\}, Gerd and Youjin Lee and Jackson Nyman and Danielle Dionne and Regan, \{Brianna M.L.\} and Vasundhara Singh and Toni Delorey and Schramm, \{Markus A.\} and Chao Wang and Antonia Wallrapp and Burkett, \{Patrick R.\} and Riesenfeld, \{Samantha J.\} and Anderson, \{Ana C.\} and Aviv Regev and Xavier, \{Ramnik J.\} and Nir Yosef and Kuchroo, \{Vijay K.\}",

note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

month = sep,

day = "13",

doi = "10.1016/j.immuni.2022.08.007",

language = "الإنجليزيّة",

volume = "55",

pages = "1663--1679.e6",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

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Pawlak, M, DeTomaso, D, Schnell, A, Meyer zu Horste, G, Lee, Y, Nyman, J, Dionne, D, Regan, BML, Singh, V, Delorey, T, Schramm, MA, Wang, C, Wallrapp, A, Burkett, PR, Riesenfeld, SJ, Anderson, AC, Regev, A, Xavier, RJ, Yosef, N & Kuchroo, VK 2022, 'Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling', Immunity, vol. 55, no. 9, pp. 1663-1679.e6. https://doi.org/10.1016/j.immuni.2022.08.007

TY - JOUR

T1 - Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling

AU - Pawlak, Mathias

AU - DeTomaso, David

AU - Schnell, Alexandra

AU - Meyer zu Horste, Gerd

AU - Lee, Youjin

AU - Nyman, Jackson

AU - Dionne, Danielle

AU - Regan, Brianna M.L.

AU - Singh, Vasundhara

AU - Delorey, Toni

AU - Schramm, Markus A.

AU - Wang, Chao

AU - Wallrapp, Antonia

AU - Burkett, Patrick R.

AU - Riesenfeld, Samantha J.

AU - Anderson, Ana C.

AU - Regev, Aviv

AU - Xavier, Ramnik J.

AU - Yosef, Nir

AU - Kuchroo, Vijay K.

PY - 2022/9/13

Y1 - 2022/9/13

N2 - Interleukin-23 receptor plays a critical role in inducing inflammation and autoimmunity. Here, we report that Th1-like cells differentiated in vitro with IL-12 + IL-21 showed similar IL-23R expression to that of pathogenic Th17 cells using eGFP reporter mice. Fate mapping established that these cells did not transition through a Th17 cell state prior to becoming Th1-like cells, and we observed their emergence in vivo in the T cell adoptive transfer colitis model. Using IL-23R-deficient Th1-like cells, we demonstrated that IL-23R was required for the development of a highly colitogenic phenotype. Single-cell RNA sequencing analysis of intestinal T cells identified IL-23R-dependent genes in Th1-like cells that differed from those expressed in Th17 cells. The perturbation of one of these regulators (CD160) in Th1-like cells inhibited the induction of colitis. We thus uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23R signaling as a pathogenic driver in Th1-like cells inducing tissue inflammation.

AB - Interleukin-23 receptor plays a critical role in inducing inflammation and autoimmunity. Here, we report that Th1-like cells differentiated in vitro with IL-12 + IL-21 showed similar IL-23R expression to that of pathogenic Th17 cells using eGFP reporter mice. Fate mapping established that these cells did not transition through a Th17 cell state prior to becoming Th1-like cells, and we observed their emergence in vivo in the T cell adoptive transfer colitis model. Using IL-23R-deficient Th1-like cells, we demonstrated that IL-23R was required for the development of a highly colitogenic phenotype. Single-cell RNA sequencing analysis of intestinal T cells identified IL-23R-dependent genes in Th1-like cells that differed from those expressed in Th17 cells. The perturbation of one of these regulators (CD160) in Th1-like cells inhibited the induction of colitis. We thus uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23R signaling as a pathogenic driver in Th1-like cells inducing tissue inflammation.

KW - IL-23

KW - IL-23 receptor

KW - T helper cell

KW - Th1-like cell

KW - autoimmunity

KW - colitis

KW - inflammation

KW - inflammatory bowel disease

KW - pre-clinical mouse model

KW - single-cell RNA sequencing

UR - http://www.scopus.com/inward/record.url?scp=85138445678&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2022.08.007

DO - 10.1016/j.immuni.2022.08.007

M3 - مقالة

C2 - 36070768

SN - 1074-7613

VL - 55

SP - 1663-1679.e6

JO - Immunity

JF - Immunity

IS - 9

ER -

Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling

Abstract

Keywords

All Science Journal Classification (ASJC) codes

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